Rationale and design of the arterial disease multiple intervention trial (ADMIT) pilot study

The primary objectives of the pilot study were to: (1) evaluate the feasibi lity of recruiting patients with peripheral arterial disease (PAD); (2) mea sure the efficacy and safety of high-density lipoprotein (HDL)-raising trea tment, low-density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic therapy, and their combinations; and (3) assess adherence t o a complex multiple drug regimen. Secondary objectives included measuremen t of the effect of the interventions on prespecified biochemical markers, m aintenance of therapy masking (in particular with niacin), and measurement of the intervention's impact on functional status and on quality of life. T o date, no secondary prevention trial has been conducted specifically among patients with PAD. Intermittent claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a striking increase in incidence of PAD w ith age, particularly among those aged >50 years in bath sexes, although me n are twice as likely as women to develop PAD. The Arterial Disease Multipl e Intervention Trial was a double-blind randomized pilot trial of 458 parti cipants with documented PAD. A 2 x 2 x 2 factorial design was used to evalu ate the effect of 3 interventions. The pilot incorporated several major nov el design features: first, the use of a simple noninvasive method (measurem ent of ankle brachial index) to identify a population with either symptomat ic or asymptomatic PAD; and second, a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as ne eded in the intervention and control group. Two other arms, the antioxidant arm (consisting of beta-carotene and vitamins E and C) and the antithrombo tic arm (using warfarin) were also added. Adherence to therapy was measured by pill count, and success in treatment was measured by the proportion of values in target range for HDL, LDL, and the international normalized ratio . (C) 1999 by Excerpta Medica, Inc.